Detection of recurrent urinary tract transitional cell carcinoma (TCC) is a frequent diagnostic challenge in exfoliative cytology because of the difficulty in distinguishing reactive changes from low grade tumors. This study evaluated the role of DNA analysis by image cytometry (ICM) as a diagnostic aid to cytology. Eighty-seven urine samples from patients with a known history of transitional cell carcinoma were examined by both cytology and ICM, and the results were compared with concurrent surgical biopsy specimens and patients' follow-up data. Twenty-seven patients were also examined by cystoscopy, and the results were compared to those of DNA analysis, cytology and biopsy. Urine samples were cytocentrifuged and stained with Papanicolaou stain for general cytology and Feulgen stain for ICM. DNA ploidy and the proliferating cell fraction (SG2M) were measured using the CAS 200 image analyzer. Among the 87 specimens included in the study, 59 were from patients considered to have recurrent disease when urine was obtained. Of the 59 recurrences, 33 were detected by cytology, 50 by ICM and 50 by biopsy, resulting in 55%, 85% and 85% sensitivity, respectively. When combined, cytology and ICM detected 53 recurrences and achieved 90% sensitivity. Nine cases originally undetected by biopsy had abnormal DNA histograms and were found to have TCC on follow-up examination. All cases undetected by ICM were low grade lesions with DNA diploidy and low proliferation. Among the 27 patients examined by cystoscopy, 14 had recurrent disease; 5, 13 and 6 of those cases were detected by cystoscopy, DNA analysis and cytology, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)